BACKGROUND: In about a third of patients with venous thromboembolism, the cause of the disorder is unexplained. In patients with atherosclerosis, activation of both platelets and blood coagulation and an increase in fibrin turnover are detectable, which may lead to thrombotic complications. Whether atherosclerosis is associated with an increased risk of venous thrombosis is unknown. METHODS: We performed ultrasonography of the carotid arteries in 299 unselected patients who had deep venous thrombosis of the legs without symptomatic atherosclerosis and in 150 control subjects. Patients with spontaneous thrombosis, patients with secondary thrombosis from acquired risk factors, and control subjects were assessed for plaques. RESULTS: At least one carotid plaque was detected in 72 of the 153 patients with spontaneous thrombosis (47.1 percent; 95 percent confidence interval, 39.1 to 55.0), 40 of the 146 with secondary thrombosis (27.4 percent; 95 percent confidence interval, 20.2 to 34.6), and 48 of the 150 control subjects (32.0 percent; 95 percent confidence interval, 24.5 to 39.5). The odds ratios for carotid plaques in patients with spontaneous thrombosis, as compared with patients with secondary thrombosis and with controls, were 2.3 (95 percent confidence interval, 1.4 to 3.7) and 1.8 (95 percent confidence interval, 1.1 to 2.9), respectively. In a multivariate analysis that accounted for risk factors for atherosclerosis, the strength of this association did not change. CONCLUSIONS: There is an association between atherosclerotic disease and spontaneous venous thrombosis. Atherosclerosis may induce venous thrombosis, or the two conditions may share common risk factors.